N - Acetylneuraminyllactosylcera - mide , GM 3 - NeuAc , a New Influenza A Virus Receptor Which Mediates the Adsorption - Fusion Process of Viral Infection

Agglutinates of native chicken erythrocytes caused by influenza virus A/Aichi/2/68 (H3Nz) at 4 OC were potently fused and lysed at low pH (optimum pH 5.3) at 37 O C . Exogenous gangliosides GMs (Siaa2-3Galj314Glcfll-ceramide) and Gm (GalNAcfll-4(Siaa2-3)Gal#ll-4Glc@l-ceramide) were integrated into the membranes of chicken asialoerythrocytes within 5min incubation at 37 O C . We found that the incorporation of ganglioside GMs containing N-acetylneuraminic acid into asialoerythrocytes restored the biological responsiveness to the virus as established by agglutination at 4 "C and fusion and hemolysis at 37 O C at pH 5.3. Biological responsiveness of GMB-NeuAe-erythrocytes to the virus was considerably higher than that of GMs-Neuce-erythrOCyteS under the same experimental conditions. Treatment of the GMS-NeuAc-erythrocytes with neuraminidase again resulted in the complete abolishment of the response to the virus. Erythrocytes containing GM2-NeuAe showed no detectable biological responses toward the virus. The above results indicate that the hemagglutinin of influenza virus A/Aichi/2/68 (HsNz) recognizes the sialyloligosaccharide chain of ganglioside GMs as its receptor which mediates the adsorption and fusion process on the virus entry into the host cells and has more preferential specificity for binding to N-acetylneuraminic acid-containing GMI than that to N-glycolyl type in the target cell membranes.